Polypeptides derived from the MHC Class I antigens have been found to increase glucose uptake in mammalian adipocytes above that obtained with maximal insulin stimulation. See U.S. Pat. No. 5,073,540, issued Dec. 17, 1991; Stagsted et al., Cell 62, 297-307 (1990). Such polypeptides have also been shown to prolong the effect of insulin and to inhibit insulin-induced internalization of the insulin receptor. These findings suggest a role for such polypeptides in the treatment of diseases such as diabetes mellitus.
The MHC Class I-derived polypeptides that are known to date, however, have several drawbacks that impede their utility. These drawbacks include low potency, instability in biological assay buffers, loss of activity after radioiodination, and gel formation. Stagsted et al., J. Biol. Chem., 266, 12844-12847 (1991 ). A need exists, therefore, for MHC Class I-derived polypeptides that maintain the desireable properties, such as increased glucose uptake, and avoid the undesireable properties, such as instability in bioassay buffers and gel formation.
To date, a tyrosyl residue at the carboxyl terminus was considered critical for the biological activity of MHC Class I-derived polypeptides. Stagsted et al., Cell, 62, at 302.